bims-stacyt Biomed News
on Paracrine crosstalk between cancer and the organism
Issue of 2019‒05‒26
four papers selected by
Cristina Muñoz Pinedo
L’Institut d’Investigació Biomèdica de Bellvitge

  1. Infect Immun. 2019 May 20. pii: IAI.00826-18. [Epub ahead of print]
    Mendez JM, Kolora LD, Lemon JS, Dupree SL, Keestra-Gounder AM.
      Nucleotide-binding oligomerization domain 1 (NOD1) is an intracellular pattern-recognition receptor (PRR) responsible for sensing bacterial peptidoglycan fragments. Stimulation of NOD1 leads to a robust innate immune response via activation of the major transcription factor NF-κB. In addition to peptidoglycan sensing, NOD1, and the closely related PRR NOD2, have been linked to inflammation by responding to the endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR). Here we show, that differential ER stress induction renders cells more susceptible to a Salmonella Typhimurium infection in a NOD1-dependent manner measured by increased NF-kB activation and cytokine expression. In HeLa57A cells, stably transfected with a NF-κB::luciferase reporter, we show that cells undergoing ER stress induced by thapsigargin display a significant increase in NF-κB activation in response to NOD1 stimulation by C12-iE-DAP and the S Typhimurium effector protein SopE. Tunicamycin-induced ER stress had no effect on NOD1 stimulated NF-κB activation. We further show that the mouse intestinal epithelial cell line MODE-K and RAW264.7 macrophages are more responsive to Salmonella infection when treated with thapsigargin but not with tunicamycin. These profound differences between thapsigargin and tunicamycin treated cells on inflammation suggest that different components downstream of the UPR contribute to NOD1 activation. We found that the NOD1-induced inflammatory response is dependent on protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) activation in conjunction with stimulation of the inositol triphosphate receptor (IP3R). Together, these results suggest that differential UPR activation makes cells more responsive to bacterial infections in a NOD1-dependent manner.
  2. Curr Opin Clin Nutr Metab Care. 2019 May 20.
    Redfern A, Agarwal V, Thompson EW.
      PURPOSE OF REVIEW: We discuss recent discoveries in hypoxic cellular pathophysiology and explore the interplay between hypoxic malignant cells and other stromal elements. This review will provide an update on the effects of hypoxia on cancer outcomes and therapeutic resistance.RECENT FINDINGS: Hypoxia has been discovered to be a key driver for tumor progression, both because of impacts on tumor cells and separately on the wider tumor microenvironment. The latter effects occur via epithelial mesenchymal transition, autophagy and metabolic switching. Through epithelial mesenchymal transition, hypoxia both drives metastasis and renders key target tissues receptive to metastasis. Autophagy is a double-edged sword which requires greater understanding to ascertain when it is a threat. Metabolic switching allows tumor cells to access hypoxic survival mechanisms even under normoxic conditions.Every element of the malignant stroma contributes to hypoxia-driven progression. Exosomal transfer of molecules from hypoxic tumor cells to target stromal cell types and the importance of microRNAs in intercellular communication have emerged as key themes.Antiangiogenic resistance can be caused by hypoxia-driven vasculogenic mimicry. Beyond this, hypoxia contributes to resistance to virtually all oncological treatment modalities.
    SUMMARY: Recent advances have moved us closer to being able to exploit hypoxic mechanisms to overcome hypoxia-driven progression and therapy failure.
  3. J Cell Biochem. 2019 May 20.
    Aftab S, Shakoori AR.
      Studying the metabolic pathways of cancer cells is considered as a key to control cancer malignancies and open windows for effective drug discovery against cancer. Of all the properties of a tumor, metastasis potential is a defining characteristic. Metastasis is controlled by a variety of factors that directly control the expression of cell adhesion proteins. In this study we have investigated the expression of cell to cell and cell to matrix adhesion protein genes during the initial phases of attachment of human glioblastoma cancer cell line SF767 (66Y old human female: UCSF Neurosurgery Tissue Bank) to the attachment surface under (Cell culture treated polystyrene plate bottom) glucose-rich and glucose-starved conditions. The aim was to imitate the natural microenvironment of glucose availability to cancer cells inside a tumor that triggers epithelial to mesenchymal transition (EMT). In this study, we have observed the gene expression of epithelial and mesenchymal isoforms of cadherin (E-CAD and N-CAD) and Ig like cell adhesion molecules (E-CAM and N-CAM) along with Integrin family subunits for the initial attachment of cancer cells. We observed that high glucose environments promoted cell survival and cell adhesion, whereas low glucose accelerated EMT by downregulating the expression level of integrin, E-CAD, and N-CAD, and upregulation of N-CAM during early period of cell adhesion. Low glucose availability also downregulated variety of structural and regulatory genes, such as zinc finger E-box binding home box 1A), cytokeratin, Snail, and β catenin, and upregulation of hypoxia-inducible factor 1, matrix metalloprotease 13/Collagenase 3, vimentim, p120, and fructose 1,6 bisphosphatase. Glucose conditions are more efficient for cancer studies in this case glioblastoma cells.
    Keywords:  cancer nutrient tolerance. cross-talk in cell adhesion molecules; cell adhesion molecules; glucose metabolism
  4. Transl Oncol. 2019 May 20. pii: S1936-5233(19)30152-4. [Epub ahead of print]12(7): 981-986
    Ribatti D, Annese T, Ruggieri S, Tamma R, Crivellato E.
      Clinical trials using anti-vascular endothelial growth factor /(VEGF) molecules induce a modest improvement in overall survival, measurable in weeks to just a few months, and tumors respond differently to these agents. In this review article, we have exposed some tumor characteristics and processes that may impair the effectiveness of anti-angiogenic approaches, including genotypic changes on endothelial cells, the vascular normalization phenomenon, and the vasculogenic mimicry. The usage of anti-angiogenic molecules leads to hypoxic tumor microenvironment which enhances tumor invasiveness. The role of tumor-infiltrating cells, including tumor associated macrophages and fibroblasts (TAMs and TAFs) in the therapeutic response to anti-angiogenic settings was also highlighted. Finally, among the new therapeutic approaches to target tumor vasculature, anti-PD-1 or anti-PD-L1 therapy sensitizing and prolonging the efficacy of anti-angiogenic therapy, have been discussed.